1. Field of the Invention
The invention is directed to controlled release formulations of solid dosage carbamazepine utilizing a cross-linked polymer or copolymer derived from one or more unsaturated carboxylic acids, which provides controlled release properties at low concentrations, while meeting acceptable release rates as specified by the United States Pharmacopeial Convention (USP).
2. Description of the Prior Art
Carbamazepine is a well-known pharmaceutical agent for the clinical treatment of seizure disorders, including tonic-clonic (grand mal) seizures, complex partial seizures and trigeminal neuralgia. Currently, however, there are a limited number of oral therapeutic systems containing carbamazepine in solid dosage form.
In U.S. Pat. No. 4,857,336 and RE 34,990 to Khanna, et al, there is disclosed a therapeutic system for peroral administration of carbamazepine. The system comprises a wall made of a material permeable to water and impermeable to the components of the drug-containing core; a core containing finely particulate carbamazepine, a protective colloid, a swellable hydrophilic polymer and an optional water-soluble compound; and a passageway through the wall for delivering the core components to the environmental body fluid. The passageway is produced by mechanical or laser drilling of the outer wall.
A drug delivery system for the oral administration of carbamazepine and a method of treating a patient with the drug delivery systems is disclosed in U.S. Pat. No. 5,326,570. The drug delivery systems consist of an immediate release unit containing carbamazepine, a sustained release unit containing carbamazepine and an enteric release unit containing carbamazepine.
In U.S. Pat. No. 5,912,013 to Rudnic, et al, there is taught a composition for treating a patient with carbamazepine in a pharmaceutical dosage form which comprises a single dosage form containing multiple units within it capable of releasing their contents at varying times, i.e., a sustained release unit and an immediate release unit.
In U.S. Pat. No. 5,980,942, there is described a zero order sustained release matrix tablet formulation of carbamazepine. The matrix tablet formulation comprises a hydrophilic polymer gel which inhibits transformation of carbamazepine into carbamazepine dihydrate and effectively changes the anhydrous carbamazepine into an amorphous form which can be released from the matrix by zero-order release kinetics.
In U.S. Pat. No. 6,294,201 an osmotic drug release system for the oral administration of a pharmaceutical agent is disclosed. The osmotic drug delivery system consists of a shell and core containing a pharmaceutically active substance, xanthan and a vinyl pyrrolidone-vinyl acetate copolymer. These water-expandable polymers allow for the release of the active substance from the shell in a controlled manner.
These prior art methods of carbamazepine delivery, however, have the inherent drawbacks of being expensive and require time-consuming methods of production. Additionally, in order to achieve and maintain a therapeutic range, a higher concentration of carbamazepine is necessary.
Solid dosage forms of immediate and sustained release tablets containing carbamazepine are formed by wet granulation or by using granules formed by wet granulation mixed with direct compression ingredients. The solid dosage form consists of a polymer or copolymer derived from one or more unsaturated carboxylic acids that is cross-linked and carbamazepine in conjunction with conventional materials such as fillers, excipients, and surface active agents. The polymer or copolymer as a controlled release agent can enhance controlled-release properties at lower concentrations than prior art systems, while meeting acceptable release rates as specified by the USP.